How deadly is Hantavirus?

Mice are wonderful creatures, which have contributed to many scientific discoveries. But they are not always helpful. It is important to remember mice are pests and can pose serious health and safety risks. This was recently highlighted in news emerging from Yosemite National Park of an outbreak of Hantavirus, a virus transmitted by mice.

I’m sure you have seen many of these headlines, but how deadly is Hantavirus?

 

Hantavirus is very rare (602 cases reported in USA in the past 20 years). However, if contracted it can be fatal in one third of cases. Symptoms can take up to 6 weeks to present and include fever, nausea, muscle aches and tiredness.

Hantavirus is spread by droppings and urine from the Deer mouse (Peromyscus maniculatus). Deer mice are found throughout North America. Upto 20% of deer mice carry the Hantavirus.

So far there has been 4 confirmed cases and 2 deaths. Approximately 4 million people visit Yosemite Park every year. Therefore the chances of contracting Hantavirus are very small. However, it is important to be aware of the risks and the initial signs of virus.

Weird Lab Mice

I found this interesting blog post, which highlights some of the weirdest mice used in research. Not exactly the most pleasant images but each mice plays an important part in scientific research.

Intrigued? Take a look…. ‘The 8 Weirdest Mice in Research’

The Nude Mouse – lacks an immune system which allows it to be used for tissue and tumor transplantation.

 

OAP Mice

I discovered a new resource this week, which seems like an excellent idea to reduce the number of mice being used in scientific research. The resource is called ShARM = Shared Ageing Research Models.

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The aim of ShARM is help researchers in the UK and oversees to have greater access to information about aged mice. They do this in two ways:

1) ShARM hold a network database of live ageing colonies. This database provides information of all the researchers currently working on aged mice and the mice they currently keep. Therefore if you have a request to study a certain mouse strain at an old age the database can put you in touch with researchers who currently have these animals and therefore share information and tissue.

2) ShARM provides a tissue bank, which acquires and stores frozen tissue from aged mice. This tissue would otherwise have been discarded but the tissue bank allows it to be given to researchers who require a certain tissue to study. For example, one researcher may have some old animals they have bred to look at the effect on the liver. They use the liver tissue for experiments then donate the other tissue to the ShARM tissue bank who store it until it is required by a researcher who is interested in another tissue.

To study ageing diseases, we need aged mouse models, which have very similar ageing processes to humans. However, to breed and keep mice until they are old is expensive and also ethically not viable. The typical life span of a lab mouse is 1.5-2 years. Therefore an experiment into ageing diseases can be a lengthy, unethical and costly procedure.

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These two facilities provided by ShARM allows the sharing of information and mice tissue, which will allow research in aged related diseases to progress at a quicker pace AND importantly reduce the amount of animals that are used in research. This is of great importance in our current climate where financial costs are putting a great strain on scientists, this facility will allow research projects to be carried out with less costs. The resource is also of great importance to the ethical dilemma of using animals in research as it raises the awareness of the 3Rs (the refinement, reduction and replacement of animals in research).

Further reading:

What are the 3Rs?

The Bruce Effect

I regularly control the breeding of mice in my day job and have always been told not to introduce a new male to the cage when the female is pregnant. Wondering why this rule existed I did some research and came across the Bruce Effect. The Bruce Effect is old news. It was first described in 1959 by Hilda M. Bruce, a British zoologist with a keen interest in rodent sexual behaviours.

The Bruce Effect describes the phenomenon of female rodents terminating their pregnancies when they are exposed to an unfamiliar male. The effect is controlled by pheromones. The pheromones secreted by the males leads to a reduction in the production of prolactin, a hormone required for progesterone production. Progesterone is required to maintain pregnancy, therefore a drop in progesterone will lead to a miscarriage. The female then ovulates and allows a new embryo to be conceived.

There are clearly evolutionary reasons why the Bruce Effect exists. How can you explain the evolutionary benefits of aborting your own offspring? One hypothesis is that the male does not want to waste its time and energy bringing up offspring who are genetically not related and therefore not containing the male’s DNA. Another hypothesis, favours the female. The male will most likely kill the offspring when they are born if they are not genetically similar. Therefore, the female doesn’t waste her energy going through the whole pregnancy and aborts sooner rather than later.

Although the effect is most commonly reported in mice, it has also been found in other species such as monkeys. I wonder what other species may possibly display the Bruce Effect? What about humans?

 

The Male Pill

A research study which received massive media coverage this week was the discover of a male contraceptive pill. If this can be successfully translated to humans the impact on society would be incredibly significant. This is why the study received a lot of press.

So what exactly was the experiment? How did they show this works? The scientists used their pharmacology knowledge to develop a drug which targets the production of sperm, which was then tested in mice.

Currently there are no drugs available as a male contraceptive, however, there are a few drugs in clinical trials which alter the amount of testosterone in the body (see NHS website). These drugs are accompanied with some worrying side effects due to the multi functional actions of testosterone in the male body. One of the biggest hurdles so far is a contraceptive pill which retains sexual desire, any hormonal drugs seem to suppress this. However, the drug reported in this study does not primarily target hormones and could therefore be advantageous.

The target of the drug in this study is the bromo- domain-containing protein (BRDT) –  a protein expressed in sperms which is essential for spermatogenesis. A small molecule called JC2 has been developed, which inhibits the activity of BRDT.  The drug JC2 was injected daily into male mice for a period of 3-6 weeks then the mice were allowed to mate with female mice.

The following findings in JC2 treated mice were observed:

– Sperm count was reduced by approximately 28%

– A significant reduction in the size of the testis

 

– Sperm mobility was reduced by approximately 4.5 fold

– The effect was reversible – stopping treatment allowed the mice to breed again

The next step is to try compounds with a higher affinity for BRDT and to study the long term effects of blocking BRDT. The successful translation of the drug from mice to humans is encouraging as BRDT is highly conserved between the two species.

The introduction of a male contraceptive pill will be interesting to follow. A few female comments suggest they wouldn’t trust their partner to be responsible and remember to take the pill. But isn’t it time we gave men the choice?

Further reading:

BBC News ‘Male contraceptive pill ‘step closer’ after mice studies’

The Guardian ‘If you sleep with a man, trust him to take the pill’

Mouse Art – Nature Medicine Aug 2012

The latest edition of Nature Medicine contains a cover photo of a mouse retina. I was drawn to this image with intrigue and wanted to know more about the web formations (in green).To understand this image you need to understand what each colour in the photo represents. In this image the following colours are represented as:

Green = isolectin B4 (marks capillary interactions)

Red = actin (marks smooth muscle cells)

Blue = DAPI (a stain used to image the nucleus of cells)

This image demonstrates angiogenesis (the growth of new blood vessels – as shown in green) in a mouse model of ischemic retinopathy (loss of vision due to insufficient blood supply). These mice have been genetically adapted to lack a gene (ATM) which prevents the formation of new blood vessels and therefore prevents the formation of tumours. This study reveals the role of ATM in angiogenesis pathways and has implications for the study of cancer and choroidal neovascularization (formation of new blood vessels in the eye).

Further reading:

Original research article – Nature 2012

 

Do-re-mi…

Leaving the lab behind, this piece of research uses a unique strain of mice found in Costa Rica called Scotinomys teguinawho are otherwise known as singing mice. They produce a high pitched singing noise, which can easily be mistaken for birdsong. The genes responsible for this unique behaviour are being used to study genes responsible for language in humans.

The gene researchers are interested in is called FOXP2. In humans, FOXP2 mutations lead to speech and language disorders. The FOXP2 gene encodes for a transcription factor, which controls the expression of other genes. Therefore, a mutation in the FOXP2 gene leads to the dysfunction of lots of other genes, which remain unknown.

This study found that neurons containing the FOXP2 gene became activated when songs from the same species were played. This shows the importance of FOXP2 in understanding vocal stimuli and the need for FOXP2 to interpret the information. The DNA from the mice is analysed and processed by a super computer to provide information on how FOXP2 plays a role in vocalisation. The importance of FOXP2 has been shown before by mice lacking the  FOXP2 gene by genetic modification, these mice show a lack of vocalisation.

Scotinomys teguin- the singing mouse from Costa Rica

So how can studying a gene in this exotic singing mouse contribute to medical research? If we can find out the role of FOXP2 in the singing mouse and its role in language, the information can be translated into humans to help cure speech disorders.

Further reading

Singing mouse video 

Function of FOXP2 in language disorders 

Green Babies

I came across this picture, which was published by Rockefeller University. These mice have a gene inserted into them which produces a protein called Green Fluorescent Protein. This protein shows up bright green when the mice are examined under a fluorescent microscope. The protein is expressed in places where actin is present, a protein found in nearly all cells and helps in lots of cellular processes, such as cell mobility, cell division and cell signalling. This protein is found throughout the body, so the whole mouse glows green.

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These mice can be used as tools for research. Their cells can be used in experimental biology and are easily tracked due to the green fluorescence.

Further reading

JAX Mouse database – Reference list of science papers using these mice in experiments.

Can you hear me squeak?

Mice have been used in a study published in Neuron to show how gene therapy can be used to cure congenital hearing loss.  Congenital hearing loss affects 12,000 infants in the US every year.  It is a type of hearing loss that occurs at birth and is in the majority of cases is due to genetics and the loss of a crucial gene. At the moment, patients are treated with a hearing aid or in severe cases a cochlear implant, which can restore some hearing. However, a cure is yet to be found. This study looked at the possibility of using gene therapy to reverse genetic mutations and restore hearing loss.

This experiment used mice bred to lack an important gene required for hearing – the gene is called Vglut3, this gene produces a protein called vesicular glutamate transporter-3. This protein is required to allow the inner ear cells to transmit sound information to the brain. These mice were therefore born with hearing loss.

To correct the loss of the gene Vglut3 – a harmless virus containing a working copy of Vglut3 was injected into the ears of the mice the day after they were born. Two weeks later the hearing in treated mice was tested. The electrical properties of the cells in the ear was tested using electrophysiology. This test shows the function of the cells had been restored and allowed sound signals to be transmitted from the ear to the brain. The structure of the cells was also studied using electron microscopy, which allowed detailed analysis of the cells needed to allow successful transmission of sound signals. Both these tests showed that gene therapy had repaired the mutant cells and hearing had been restored in the mice

This is great news and very encouraging. The hope is that this can be translated into a clinical trial and a treatment for babies born with congenital hearing loss. Unfortunately, the mice used did not have the same genetic mutation as seen in humans, which the authors explain by the fact they only had access to these mice in their lab at the time of the experiment. Hopefully these positive results can be replicated in mice with the same genetic mutation as humans.

Further reading

Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy – Neuron July 2012

Gene therapy to restore hearing sounds closer to reality after success in deaf-born mice – Spoonful of Medicine July 2012